Rationale and background
Finasteride is a specific inhibitor of 5a-reductase, an enzyme that converts testosterone into dihydrotestosterone. It is approved in Europe for treating benign prostatic hyperplasia (BPH) at 5 mg and androgenetic alopecia at 1 mg and 2.275 mg/dl. Dutasteride, another 5a-reductase inhibitor, is also approved in Europe for moderate-to-severe BPH, either alone or in combination with tamsulosin. In some non-EEA countries, dutasteride is also used for androgenetic alopecia.
Signals of mood changes, including depressed mood, depression, and rarely suicidal ideation, have been reported in patients using finasteride. Depression is listed as a side effect of finasteride, along with anxiety and suicidal thoughts, though their frequency is unknown. These psychiatric effects were not identified during clinical trials but were later explored in post-marketing observational studies. There is insufficient data in the literature regarding the background rates of suicide related events in these populations.
The aim of this study is to evaluate the background/incidence rates of suicide-related events in adult male patients exposed to finasteride or dutasteride medicines for the conditions of androgenetic alopecia and BPH. Having background rate data would be helpful to contextualise review and to give some insight into the impact of the indication on suicide-related events. Further understanding of the safety of these medicines regarding their potential psychiatric effects can help inform regulatory decisions and the assessment of the benefit/risk profile of these medicines.
Research question and objectives
Research question
What are the background/incidence rates of suicide-related events in the general adult male population, adult males with newly diagnosed androgenetic alopecia, and benign prostatic hyperplasia, overall and by age group?
Objectives
The objectives are to evaluate the background/incidence rates of suicide-related events overall and by age group (10-year age bands) in:
1. The general adult male population.
2. Adult males with newly diagnosed androgenetic alopecia.
3. Adult males with newly diagnosed androgenetic alopecia stratified by treatment (finasteride, dutasteride, topical minoxidil, spironolactone).
4. Adult males with newly diagnosed benign prostatic hyperplasia (BPH).
5. Adult males with newly diagnosed BPH stratified by treatment (finasteride, dutasteride, alpha
blockers, tadalafil, saw palmetto).
Methods
Study design
Population level cohort study.
Population
The study population will include all adult male population (= 18 years) present in the data source during the study period. (objective 1).
Within this population 2 sub-cohorts will be nested namely one of adult male patients newly diagnosed with androgenetic alopecia and one consisting of adult male patients newly diagnosed with BPH (objectives 2 and 4).
Within these cohorts of adult males newly diagnosed with androgenetic alopecia and BPH, we will nest cohorts of individuals initiating treatments of interest for the first time in the study period (objectives 3 and 5).
Study period
Study period may vary between data sources and will start at the earliest date of data-availability of the respective DP until the end of available data; and with at least 365 days of database history prior to index date.
Variables
Outcomes:
Outcomes of interest are i) completed suicide (condition record of suicide plus death date in the following 30 days), ii) attempted suicide, iii) suicide ideation, iv) intentional self-harm, v) composite outcome(combination of any of the above-mentioned events).
Relevant covariates
Age groups (10-year age bands), type of treatments (i.e. finasteride, dutasteride, topical minoxidil, alpha blockers, spironolactone, tadalafil, saw palmetto).
Data source
1. Clinical Practice Research Datalink (CPRD) GOLD, United Kingdom
2. Danish Data Health Registries (DK-DHR), Denmark
3. InGef Research Database (InGef RDB), Germany
4. Integrated Primary Care Information (IPCI), Netherlands
5. Croatian National Public Health Information System (NAJS), Croatia
6. The Information System for Research on Primary Care (SIDIAP), Spain
Sample size
No sample size has been calculated as this is a descriptive disease epidemiology study where we are interested in the incidence rates of suicide-related events in adult male patients diagnosed with androgenetic alopecia or BPH in each data source, irrespective of the sample size.
Statistical analysis
Yearly incidence rates of suicide-related events per 100,000 person-years (PYs) will be estimated in the general population of adult males, the adult male patients diagnosed with androgenetic alopecia or BPH.
Within these populations, incidence rates of suicide-related events per 100,000 PYs will also be calculated for the drug exposures of interest (i.e. respective treatment of BPH or androgenetic alopecia). Yearly incidence rates will be reported overall and stratified by age categories and type of treatments. Incidence rates will be given together with 95% Poisson confidence intervals. The statistical analyses will be performed based on OMOP-CDM mapped data using “IncidencePrevalence” R package. A minimum cell counts of 5 will
be used when reporting results, with any smaller count reported as “<5”.